The research proposed here is designed to compare the relative severity of neurotoxicity produced in rats by the hypoxic cell radiosensitizers misonidazole and desmethylmisonidazole, and, because electrophysiologic tests have been shown in a rat model to be an excellent measure of central and peripheral neurotoxicity produced by the two radiosensitizers, to evaluate the efficacy of the tests as a measure of neurotoxicity in a group of patients harboring central nervous system tumors who are undergoing radiation therapy with and without the concomitant administration of the radiosensitizing agents. Specifically, our experimental research will use nerve trains analysis to compare the peripheral neurotoxicity produced in rats by the two agents, use brain stem evoked potentials and cortical evoked potentials to compare the central neurotoxicity produced in rats by the two agents, attempt to modify this neurotoxicity in rats with phenytoin, corticosteroids, and diuretics, and correlate neuropathologic features with the electrophysiologic findings in rats treated with the two agents. We will also test the neurotoxic effects of the two agents at repeat challenge. In our clinical research, using the electrophysiologic tests we will evalute peripheral and central neurotoxicities produced in patients by desmethylmisonidazole, evalute with brain stem auditory evoked potentials and cortical evoked potentials the central neurotoxicity produced in patients by cranial irradiation only and by concomitant administration of desmethylmisonidazole, and attempt to correlate our clinical findings with the results of our experiments in rats. Our experimental methodology will include serial determination of electophysiologic test parameters and plasma pharmacokinetic parameters, and correlation of electrophysiologic test results to histopathologic data obtained at sacrifice in groups of rats treated on a standard protocol with the two agents. Our patient population will be followed with the electrophysiologic tests, by plasma pharmacokinetic determinations, clinical examination, and computerized tomographic and radionuclide brain scans (where applicable). The results obtained in the experimental and clinical research will be compared to evaluate the efficacy of the electrophysiologic tests as a measure of neurotoxicity in humans, and to define the relative severity of neurotoxic effects produced by the two radiosensitizing agents in rats.